Customized nutritional therapies offer real solutions for the symptoms and complications associated with diabetic neuropathy. Diabetic neuropathy is the result of the long term effect of poor glycemic control and type 2 diabetes mellitus.
In the United States alone, according to 2012 statistics, approximately 9.3% of the population is diabetic, and another 37% of the population is pre-diabetic. Type 2 diabetes is a condition that is preventable and effectively treatable through nutritional means.
Not only can nutritional therapies effectively manage type two diabetes, but nutrition can also be used to effectively treat the complications of diabetes mellitus. This includes the use of:
- Individualized diet
- Nutrient therapies such as vitamins and minerals
- Herbal medicine
- Lifestyle factors such as exercise and sauna therapy
Diabetic neuropathy is the result of the long term struggles with diabetes. It is a painful series of complications that involves nerve damage, damage of organ function, especially to the kidneys, retina, and peripheral tissues.
4 Biochemical Pathways Most Responsible for Diabetic Neuropathy
When blood sugar fails to get taken up into the cells, metabolism inside of the cells is severely compromised. This process of erratic and ineffective glucose utilization results in numerous inflammatory and toxic processes. These inflammatory processes are responsible for diabetic neuropathy, as well as the cardiovascular disease complications that are inevitably a result of these processes.
Hexosamine Pathway – This pathway involves the formation of glucosamine-related by-products. The elevated production of n-acetyl glucosamine from glucose can result in various glycoproteins, proteoglycans and glycolipids, which create oxidative damage and toxicity (1, 2).
Polyol Pathway – the Polyol pathway is normally inactive because healthy people without diabetes can metabolize blood sugar just fine. The story is quite different for diabetics with insulin resistance (3, 4).
Our muscles, abdominal fat tissue (called adipose) and certain organs require insulin for normal glucose transport into those cell types. However our nerves, retinas, and kidneys don’t require insulin in order for glucose to be made available in those tissues. That means when glucose levels are elevated, the nerves, kidneys and retina passively take up glucose in an unlimited fashion. This results in the activation of the polyol pathway.
The polyol pathway results in the formation of sorbitol, a type of toxic sugar that causes glycation (stickiness) of protein molecules. This process of glycation results in the formation of advanced glycation end products (AGEs). AGEs are one of the main causes of diabetic neuropathy, including the induction of noxiously inflammatory processes that damage our cardiovascular system.
In addition to sorbitol formation, the polyol pathway produces fructose directly from sorbitol. One of the main problems with increased levels of fructose is that it increases uric acid. At high enough levels fructose inhibits nitric oxide, which results in endothelial dysfunction and blood vessels that can’t properly dilate. At high enough levels, Uric acid is also known to precipitate into joints causing gout.
We can actually divert our cells from producing sorbitol. This is sometimes referred to as the “AGE shunt”. The fat soluble form of vitamin B-1 known as benfotiamine does just this. Benfotiamine diverts metabolites that form sorbitol towards another pathway known as the pentose phosphate pathway. It’s for this reason that repeated studies have found benfotiamine to be effective at improving diabetic neuropathy complications as well as shunting sorbitol. An assortment of other nutrients and herbs have shown the ability to shunt AGE formation as well This includes: alpha lipoic acid, and pyradoxamine (unfortunately not currently available in the US).
Not only does the powerful antioxidant alpha lipoic acid divert AGE formation, it improves motor nerve conduction velocity, increases GLUT-4 uptake of glucose and protects from Ischemic stroke. Alpha lipoic acid also has been shown to activate AMPK, increase fatty acid oxidation and prevents fatty liver
Diaglycerol Protein Kinase C (DPKC) – Activation of this pathway results in inflammatory proteins such as NF kappa beta (5). The result of the activation can make the vascular endothelium excessively permeable (6), as well as cause white blood cells to clump (7). These are very bad circumstances.
Peroxynitrite formation – peroxynitrites are powerful oxidants which are at play with most significant tissue destructive processes, including diabetic neuropathy (8). Peroxynitrites form as a result of the interaction between the free radical superoxide with the blood vessel-dilating free radical nitric oxide. When nitric oxide is oxidized excessively, the endothelium becomes a net producer of superoxides.
When formed, peroxynitrite inactivates our important antioxidant cellular defenses such as glutathione as well as oxidizes our co-enzyme Q10. The result of peroxynitrite is severe cellular toxicity, and any number of destructive outcomes.
Nutrients & Herbs: Glucose Utilization
The cornerstone of an effective nutritional strategy for those with type 2 diabetes mellitus involves controlling serum glucose. This involves supporting the function of a number of important cellular processes. The following is a short list of two of these processes, as well as nutrients and herbs which have been shown to attenuate these processes.
- Stimulation of the GLUT-4 transporter: GLUT-4 is the key glucose transporter in muscle and fat cells. It is essentially what enables extracellular glucose to diffuse into cells. Modulating GLUT-4 is fundamental to the process of enhancing glucose utilization. Significant GLUT-4 stimulating compounds include: Berberine (9, 10), Bitter melon (11, 12), alpha lipoic acid (13, 14), Ginseng (15) and Chromium (16).
- Activation of AMPK: AMP-activated protein kinase is a metabolic regulating switch in cells, which “turns on” essential metabolic processes, increases fat burning, activates the migration of the GLUT-4 vessicle, modulates fatty acid oxidation, and attenuates numerous intracellular signaling processes. Notable AMPK activators include: Exercise, caloric restriction, alpha lipoic acid (17, 18), salvia miltiorrhiza (19, 20), berberine (9, 10), gynostemma (21), Chromium (22).
Nutrients & Herbs: Diabetic Complications & Neuropathy
There are a wide variety of nutrients and herbs which have been shown to mitigate the potentially deadly effects of nerve, organ and tissue damage and necrosis, which is the result of hyperglycemia. Below is a short list of the most notable.
- Benfotiamine – Inhibits 3 major pathways which cause diabetic damage (23). This fat-soluble form of thiamine effectively shunts the pathways most responsible for glucose-induced damage. One of its protective mechanisms acts by shunting glyceraldehyde -3- phosphate and fructose-6-phosphate away from glycolysis and towards the pentose phosphate pathway (24). Benfotiamine has been shown highly effective in the treatment of diabetic neuropathy (25, 26), as well in preventing the formation of Advanced glycation end products (AGEs) (27, 28).
- Pyridoxamine – This is an analogue of Vitamin B-6. It is currently not available in the US, but is available in the UK. Pyridoxamine traps AGEs and is a potent free radical inactivator (29, 30 31).
- L-Carnosine – This potent amino acid also possesses strong AGE (advanced glycation end products)-inhibiting actions (32) as well as improving endothelial function (33).
- Salvia miltiorrhiza – This ancient Chinese herb known as “Dang shen” or “red sage root” has some remarkable properties. Various constituents of this herb such as lithospermate B has been shown to inactivate peroxynitrite, a potent oxidant responsible for vascular damage (34). Additionally, salvia increases nitric oxide expression (35), especially in kidneys and the aortic endothelium (37). Dang shen also reduces white blood cell adhesion (36) and platelet aggregation (39). Most remarkable: in rats constituents of salvia has shown to increase kidney glutathione and SOD expressions (38).
- Alpha Lipoic Acid – This potent sulfur-containing antioxidants has showed up under numerous benefits for diabetics. Lipoic acid has the unique ability to function as an antioxidant in both its reduced and oxidized states. Lipoic acid provides protection following brain ischemia (40). It has the unique ability to activate glutathione (41), one of the most critical cellular antioxidants. Together with benfotiamine, alpha lipoic acid effectively improves symptoms of diabetic neuropathy (42).
- Korean red ginseng – This potent form of ginseng has shown effective at alleviating AGE-induced damage to kidneys (43) as well as improving endothelial function (44). Korean red ginseng has also been shown to protect cells from the toxic effects of peroxynitrite (45).
- Honorable mentions: Glutathione supplementally is certainly worthy of discussion, because it is a powerful free radical scavenging antioxidant. The best forms supplementally would be liposomal. BH4 (biopterin) is a key molecule that stimulates the nitric oxide synthase enzyme (NOS) for nitric oxide production. BH4 is not currently available in supplemental form.
In conclusion, nutrient and herbal therapies offer powerful solutions for the many problems associated with type 2 diabetes mellitus, including complications of polyneuropathy, and vascular-related injuries.